Chronic kidney disease (CKD) is highly morbid, and it affects race/ethnic minorities disproportionately. Early detection and treatment are the cornerstones of prevention epidemiology. Yet to date, there is no consensus for CKD screening among persons without diabetes. The current clinical strategy among non-diabetics relies on serum creatinine for diagnosing CKD, and this strategy misses many persons at risk. In fact, 1 in 6 adults in the U.S. may have undetected CKD despite having creatinine measured. Serum creatinine is biased by age and race, which results in the inability to reliably detect CKD across age and race/ethnic groups. Despite the availability of an established marker of kidney injury such as albumin-to-creatinine ratio (ACR) and an alternative filtration marker, cystatin C, these are not routinely recommended or used in general clinical practice. These markers have been shown to improve CKD risk stratification, but their utility in CKD screening is not known. ACR and cystatin C can detect CKD that is missed by creatinine (occult CKD) in up to 16% of U.S. adults. Persons with occult CKD are at high risk for death, cardiovascular events and progression to ESRD. The use of a triple marker approach of creatinine, cystatin C, and ACR to detect CKD has not been studied. Moreover, the absence of evidence to determine who would benefit most from CKD screening prohibits investigation of targeted screening programs. Without effective screening programs, our ability to detect CKD and to design and evaluate prevention strategies is limited. This application proposes a paradigm shift in the field of CKD prevention by developing the knowledge necessary to design, evaluate and implement effective CKD screening strategies across diverse populations. Specifically, we propose to pool data from four large, ongoing, NIH-funded cohorts that represent over 27,000 Black and White persons aged 28-84: the Coronary Artery Risk Development in Young Adults (CARDIA), Multi-Ethnic Study of Atherosclerosis (MESA), Reasons for Geographical and Racial Differences in Stroke (REGARDS), and the Health, Aging and Body Composition (Health ABC) Studies. We propose to use these pooled data to implement a triple marker approach to investigate the prevalence of occult CKD among non-diabetics. We will evaluate the numbers needed to screen to detect occult CKD by cystatin C or ACR. Our second goal is to evaluate risk factors associated with occult CKD overall and by age, sex and race/ethnicity. We will then develop a prediction tool for occult CKD and a clinician-friendly, online calculator to estimate an individual's probability of having occult CKD. The data generated from these projects can directly lead to the evaluation of screening strategies that are targeted to individual risk. PUBLIC HEALTH RELEVANCE: Early detection of CKD may improve our ability to implement prevention programs, yet there is no consensus regarding CKD screening among adults without diabetes. The current strategy for detecting kidney disease in non-diabetics is narrowly focused, and misses a large proportion of affected individuals. This proposal envisions the use of three markers to detect kidney disease in persons deemed to be at high risk for having CKD that may be missed by current clinical practice. The knowledge gained from this proposal could change the way we screen for CKD and allow implementation of prevention strategies.